Oxidation of heterocyclic aromatic nitrogen compounds



Patented Feb. 24,

OXIDATION OF HE TEROCYCLIC AROMATIO NITROGEN COMPOUNDS Max B. Mueller, Dcmarest, N. .L, assignor to Allied Chemical & Dye Corporation, New York,

N. Y., a corporation or New, York No Drawing. Application October 9, 1942,

Serial No. 481,446

21 Claims.- (01. zoo-295.5)

This invention relates to the catalytic oxidation to pyridine carboxylic acids of heterocyclic aromatic nitrogen compounds having an oxidizable organic grouping attached to the nitrogenmore carbon-to carbon linkages which may be treated in accordance with this invention are the picolines, the lutidines, the collidines, quinoline, hydroxyquinolines, quinoline sulfonic acids, isocontaining aromatic nucleus by one or more 5 qul e, qui a i pid and nicotine In carbon-to-carbon linkages; more particularly, it every case it ha been found t such reiates to the production of nicotinic acid from sta ces up bei Subjected t0 treatment in compounds of this type. cordance with my invention yield pyridinecar- The present need of plentiful supplies of the oxylic acids; an imp r ant f t f my i vitamin B complex for proper nutritional requirevention is. that it permits the Production of the ments has greatly increased th importance 0f highly valuable nicotinic acid in good yields from producing suitable quantities of nicotinic acid, readily avai a u oline or pi in My member of th vitamin B l from n t. invention, therefore, has not only succeeded in erocyclic aromatic nitrogen compounds obtainma a eap oxidizing a e t. na y, S u able from coal tar having anoxidizable organic l5 acid, available for the production of valuable aromatic nitrogen-containing compounds having an oxidizable organic grouping attached to the.

nitrogen-containing aromatic nucleus by one or .more carbon-to-carbon linkages. A more specific object of this invention is to provide a simple and practical process for the preparation of nicotinic acid from inexpensive heterocyclic aromatic nitrogen compounds such as quinoline or 3-picoline.

I In accordance with this invention an N-het- .e'roaryl compound having an oxidizable organic grouping attached to the nitrogen-containing aromatic nucleus by one or more carbon-to-carbon linkages is oxidized to a pyridine carboxylic acid with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound. The selenium compound, it has been found, catalyzes oxidation of the N-heteroaryl compound with sulfuric acid so that good yields of the desired pyridine carboxylic acid may be obtained. The selenium compound may be incorporated in the reaction mixture by adding thereto uncombined selenium or a selenium compound soluble in the sulfuric acid reactant. Among the N-heteroaryl compounds having an oxidizable organic grouping attached to the hitrogen-containing aromatic nucleus by one or pyridine carboxylic acids, but has provided a comparatively cheap method of preparing nicotinic acid.

The term "N-heteroaryl compound is employed throughout the specification and claims to denote a heterocyclic compound formed by the replacement of one l 7 group of an aromatic nucleus by a nitrogen atom.

As hereinabove pointed out, my invention is applicable to the oxidation of any N-heteroaryl compound having an oxidizable organic group-v ing attached-to the nitrogen-containing aromatic nucleus by one or more carbon-to-carbon linkages. The nature of theproduct obtained will vary, depending upon the particular com pound treated. Thus, for example, the oxidation of 3-picoline, 2,3-lutidine, quinoline, 8-hydroxyquinoline, quinoline-8-sulfonic acid, quinaldine or nicotine in accordance with this invention yields the highly valuable nicotinic acid, thus making possible theproduction of this material from a wide variety of N-heteroaryl compounds. 0xidation' of 2-picoline yields picolinic acid, whereas oxidation of 4-picoline yields isonicotinic acid; oxidation of isoquinoline yields cinchomeronic acid. A preferred embodiment of my invention involves the oxidation of quinoline or 3-picoline to nicotinic acid since the quinoline or 3-picoline reactants are readily available and the product obtained is the most valuable of the pyridine carboxylic acids at the present time. The N-heteroaryl compounds treated may be in substantially pure condition, or in crude form as recovered from coal tar by fractionation.

The sulfuric acid employed is preferably concentrated sulfuric acid such as 66 B. acid, but more dilute acid such as B. acid may be used, or, less desirably, fuming sulfuric acid. The amount of sulfuric acid employed may vary somewhat, depending upon the nature of the N-heteroaryl compound treated: thus, for example, production of nicotinic acid from quincline theoretically requires mols of sulfuric acid per mol of quinoline, 9 mols being required for the acutal oxidation and 1 mol for neutralization of the basic nitrogen atom of the product, whereas oxidation of 3-picoline theoretically requires only 4 mols of sulfuric acid per mol of 3-picoline, 3 mols being for the actual oxidation. Generally, the amount of sulfuric acid employed should be between about 33% and about 100% in excess of that theoretically required for the oxidation.

The selenium compound which acts as the catalyst may be incorporated in the reaction mixture in any suitable manner. Thus, for example, uncombined selenium may be added directly to the sulfuric acid, or selenium oxychloride, selenium oxybromide, selenium sulfoxide, selenic acid or its salts, selenium dioxide or selenous acid or metal salts theerof may be added to the reaction mixture. The selenium catalyst may advantageously be prepared by slowly adding a slight excess of nitric acid to selenium and then boiling the mixture for about fifteen minutes to form a selenium dioxide solution and effect the removal of excess nitric acid; sulfuric acid may also be usrd to convert selenium into the dioxide, althou h the temperatures required in this instance are considerably higher than when nitric acid is used. The amount of catalyst employed may vary widely, but generally between about 0.03 and 0.3 gram atom of selenium per mol of N-heteroaryl compound treated is suitable.

The oxidation may be carried out by mixing the reacting ingredients and the selenium catalyst in the proportions above indicated and heating the mixture at elevated temperatures, e. g..

between about 200 and about 325 C., for a time sufficient to accomplish the desired oxidation, preferably in a vessel provided with an air condenser through wh ch gases evolved from the reaction mixture must pass so that selenium escaping with the sulfur dioxide produced by the reaction may be returned to the reaction mixture. Oxidation of quinoline to nicotinic acid is preferably carried out at a temperature between about 295 and 315 C. and oxidation of 3-p coline at from about 305 to about 315 C. The time necessary for carrying out the reaction may vary considerably, but usually between about six and about twenty-four hours, preferably between about eight and about twelve hours, are sufficient.

The oxidation process of my invention, however, is preferably carried out by heating a mixture of the major portion, e. g., approximately 70%, of the sulfuric acid and about half the amount of the selenium compound catalyst to a temperature between about 200 and about 325 C. and gradually adding a mixture of the remainder of the sulfuric acid and catalyst and the N-heteroaryl compound to be oxidized to the hot mixture in the reaction vessel, while maintaining the temperature of the mixture within the above range. After addition of the N- heteroaryl compound has been completed, the mixture may be heated at a temperature within the above range, preferably in a vessel provided with an air condenser, for an additional period of time, c. g., for from two to twenty hours, in order to complete the oxidation. This method whereas in a process in which the entire amounts of the reactants are mixed at the start of the reaction the tendency'of the catalyst to distill from the reaction mixture sometimes results in too little catalyst being present in the reaction mixture at the end of the reaction.

The pyridine carboxylic acid product obtained as a result of the oxidation may be recovered in y suitable manner. In the case of nicotinic acid, produced in accordance with the preferred embodiment of this invention, the acid reaction mixture containing sulfuric acid, nicotinic acid sulfate and the selenium catalyst may be cooled to room temperature and poured into ater or ice; the sulfuric acid may then be partially neutralized with an alkaline material such as ammonia and the selenium precipitate which forms removed by filtration. The pH value of the solution may then be raised to between about 5 and about '7 by adding sufficient alkali, or by adding an excess of ammonia thereto and boiling until the solution becomes acid to litmus, and the nicotinate converted into copper nicotinate by reaction with copper sulfate; the copper nicotinate precipitate may be recovered by filtration and converted by reaction with sodium hydroxide into sodium nicotinate. Nicotinic acid is preferably recovered from the sodium nicotinate by the addition of an acid such as hydrochloric or sulfuric acid to the sodium nicotinate solution until the pH value thereof is between about 3 and about 4, preferably between about 3.4 and about 3.6, and cooling, since I have found maximum yields of nicotinic acid may thereby be obtained; a Brom Phenol Blue indicator maybeused in adjusting the pH value since the neutral point of this indicator to nicotinic acid, 1. e., the point at which the indicator just turns yellow, is within the ranges above mentioned. The nicotinic acid mayalso be recovered by decomposing the copper nicotinic with hydrogen sulfide, separating the copper sulfide and recovering the nicotinic acid from the filtrate.

Cinchomeronic acid may be advantageously recovered from the reaction mixture resulting from oxidation of isoquinoline by cooling-the mixture, partially neutralizing to precipitate the selenium catalyst, adjusting the pH value of the solution to between 1 and 2, preferably between 1.4 and 1.6, and crystallizing the acid.

The following examples are illustrative of my invention. Amounts are given in parts by weight.

Example 1.-4.8 parts of selenium oxychloride were dissolved in 920 parts of 95% sulfuric acid and the mixture heated to 300 C. in a vessel provided with an air condenser. To this solution was gradually added a mixture of parts of pure quinoline, 4.8 parts of selenium oxychloride and 370 parts of sulfuric acid, the addition being carried out over a period of three and a half hours and the temperature being maintained at 300 C. At the end of this time has the advantage of avoiding substantial sul- Ionation of the N-heteroaryl compound, a reacthe reaction mixture was heated at 300 C. for an additional three hours and was then permitted to cool to room temperature. The cooled reaction mixture was poured into 2,000 parts of crushed ice, 630 parts of a 28% ammonia solution were added thereto, the selenium precipitate recovered by filtration and the filtrate boiled for twenty minutes with 20 parts of decolorizing carbon and nicotinate was boiled for fifteen minutes and filtered hot. The copper nicotinate filter cake was washed with hot water and then dried at 120 C.

62 parts of the copper nicotinate prepared as above described were boiled for thirty minutes with a solution of 20 parts of sodium hydroxide in 350 parts of water. At the end of this time the 1 hot slurry was filtered and the copper oxide filter cake washed with boiling water, the wash water being combined with the filtrate. The combined filtrate and washings were then concentrated by boiling, and the nicotinic acid liberated from the sodium nicotinate contained therein by the addition of sufilcient concentrated hydrochloric acid to make the solution neutral to Brom Phenol Blue. The resulting slurry of nicotinic acid was cooled to about C. and maintained at this temperature for one and a half hours, at the end of which time the nicotinic acid was recovered by filtration. The product was washed with cold water and dried at 80 0., whereby nicotinic acid, melting at 235 C., was obtained.

Example 2.-85 parts of pure quinoline, 4.8 parts of selenium oxychloride and 920 parts of 95% sulfuric acid were mixed and heated in a vessel provided with an air condenser at a temperature between 285 and 295 C. for seven hours. At the end of this time the mass was permitted to cool to room temperature. Nicotinic acid was recovered from the reaction mixture as described in Example 1.

Example 3. 85 parts of pure quinoline, 2 parts of selenium and 920 parts of 95% sulfuric acid were mixed and the mixture heated in a vessel provided with an air condenser at a temperature between 285 and 295 C. for seven hours. At the end of this time the mass was permitted to cool to room temperature. Nicotinic acid was recovered therefrom as described in Example 1.

Example 4.A solution of 1.89 parts of selenous acid and 85 parts of quinoline in 370 parts of 95% sulfuric acid was added to a solution of 2.85 parts of selenous acid in 920 parts of 95% sulfuric acid over a period of four hours, the temperature being maintained between 300 and 305 C. The reaction mixture was then maintained at a temperature within this range for an additional four and a half hours. The nicotinic acid produced was recovered from the reaction mixture as described in Example 1.

Example 5.A solution of 14.6 parts of selenium oxychloride and 255 parts of quinoline in- 1650 parts of 95% sulfuric acid was added dropwise to a solution of 0.85 part of selenium in 920 parts of 95% sulfuric acid over a period of twelve hours, the temperature being maintained between 300" and 305 C. The reaction mixture was then maintained at a temperature within this range for an additional four hours. Nicotinic acid produced was recovered as described in Example 1.

Example 6.-62 parts of 3-picoline, 5 parts of selenium oxychloride and 413 parts of 95% sulfuric acid were mixed and heated in a vessel provided with an air condenser at a temperature between 305 and 315 C. for fourteen hours.

'At the end of this time the reaction mlxturewas permitted to cool to room temperature, the mass poured into water and the resulting solution made slightly alkaline by the addition of ammonium hydroxide. Upon making the solution alkaline, the unreacted 3-picoline layer separated; selenium, which also separated, was recovered by filtration. The aqueous layer was then heated with 1% by weight of decolorizing a vessel provided with an air condenser to a temperature of 270 C. The temperature of the reaction mixture was then gradually raised to 310" C. over a period of four hours and maintained at this value for an additional seven hours. At the end of this time the mixture was permitted to cool to room temperature, poured into water and ammonium hydroxide added to the solution until it became alkaline. When the solution became alkaline, unreacted 2,3-lutidine separated out and was removed by decantation; selenium, which also separated out, was recovered by filtration. The solution was then extracted with benzene to remove residual unreacted lutidine, and the extracted solution treated with 1% by weight of decolorizing carbon and filtered hot. The filtrate was boiled to remove the excess ammonia, 84 parts of CuSO4.5H2O were added thereto, and the copper nicotinate precipitate filtered oil. The copper nicotinate filter cake was washed with water and then heated for one hour with 240 parts of a 5N sodium hydroxide solution. The suspension thus formed was heated with 1% of its weight of decolorizing carbon, filtered hot, the filtrate made neutral to Brom Phenol Blue with hydrochloric acid and permitted to stand at 5 C. for six hours. The nicotinic acid precipitate which formed was filtered, washed with water and dried.

Example 8.920 parts of 95% sulfuric acid and 4.8 parts of selenium oxychloride were mixed and heated in a vessel provided with an air condenser to between 300 and 305 C. A mixture of 95.6 parts of s-hydroxyquinoline (M. P. 74 C.) and 368 parts of 95% sulfuric acid was then gradually added to the hot solution over a period of four hours, the solution being maintained at a temperature between 300 and 305 C.; the reaction mixture was then heated for an additional three hours at a temperature within this range. At the end of this time the mass was permitted to cool to room temperature, poured over ice, and ammonium hydroxide added thereto in amount sufilcient to neutralize 90% of the free sulfuric acid; the selenium which separated was recovered by filtration, 20 parts of decolorizing carbon were added to the filtrate and the mixture boiled for thirty minutes and filtered hot. The filtrate was made neutral to Brilliant Yellow by adding ammonium hydroxide and was then boiled with 20 parts of decolorizing carbon and filtered hot. The filtrate was heated to boiling and a substantially saturated hot aqueous solution containing parts of CllSO4.5H2O was added thereto. The copper nicotinate slurry formed was boiled for thirty minutes and. the copper nicotinate then filtered therefrom. washed and dried. The dry copper nicotinate was boiled for one-half hour with a solution of 25 parts of sodium hydroxide in 600 parts 01 water. and the resulting slurry boiled for an additional half hour with 10 parts oi decolorizing carbon and filtered hot; to the filtrate was added hydrochloric acid until the mixture was neutral to Brom Phenol Blue. The mixture was then cooled to between and 10 C., maintained at this temperature for one hour and the nicotinic acid which separated recovered by filtration.

Example 9.-920 parts oi 95% sulfuric acid and 4.8 parts of selenium oxychloride were mixed and heated in a vessel provided with an air condenser to a temperature between 800 and 305 C. A mixture of 138 parts of quinoline-B-sulionic acid and 388 parts of 95% sulfuric acid was gradually added to the hot solution over a period of about four hours while maintaining the mixture at a temperature between 300 and 305 C.; the reaction mixture was then heated for an additional three hours at a temperature within the above range. Nicotinic acid was recovered from the reaction mixture as described in Example 1.

Example 10.109 parts of nicotine, 6 parts of selenium oxychloride and 2300 parts of 95% sulfuric acid were mixed and heated rapidly in a vessel provided with an air condenser to a temperature of 260 C.; the temperature of the mass was then gradually raised to about 320 C. over a period of seven hours, maintained at 320 C. for nine hours and then raised to 340 C. and held at this level for an additional ten hours. At the end of this time the reaction mixture was cooled, poured into ice and neutralized with ammonia; the unreacted nicotine which formed a separate layer upon neutralization was removed. the selenium precipitate filtered off andthe aqueous layer extracted with benzene to remove residual unreacted nicotine. The acqueous solution was then heated with 1% of its weight of decolorizing carbon, filtered hot. and 64 parts of CuSOe.5HzO were added to the filtrate. The excess ammonia was then removed from the solution by boiling and the precipitated copper nicotinate recovered by filtration. Nicotinic acid was isolated and recovered as described in Example 1.

Example 11.-62 parts of Z-picoline, 410 parts of 95% sulfuric acid and 5 parts of selenium oxychloride were mixed and the mixture heated for six hours at 320 C. in a vessel provided with an air condenser. At the end of this timethe reaction mixture was permitted to cool and was poured over ice. 98% of the free acid was then neutralized with ammonium hydroxide and the selenium which precipitated was removed by filtration; the filtrate was boiled for one-half hour with decolorizing carbon, filtered hot and made alkaline with an excess of ammonium hydroxide. On making the filtrate alkaline, unreacted 2- ,oicoline separated therefrom and was removed by decantation; the residual unreacted 2-picoline remaining in the solution was recovered by extraction with benzene. The extracted aqueous solution was then heated to boiling and a substantially saturated solution of copper sulfate added thereto. The copper picolinate slurry formed was boiled for one-half hour, and the copper picolinate filtered therefrom, washed with water and dried. The copper picolinate was then suspended in hot water and hydrogen sulfide gas was passed into the suspension for fifteen-minutes: at

the end of this time decolorizing carbon was added Example 12.93 parts or 4-picoline, 7 parts 0! selenium oxychloride and 620 parts of 95% suli'uric acid were mixed and heated at a temperature of about 310 C. for seven hours in'a vessel provided with an air condenser. At the end of this time the reaction mixture was permitted to cool to room temperature and was poured into 750 parts of water. The selenium which separated at this point was removed by filtration. The filtrate was neutralized with a slight excess of ammonium hydroxide, 126 parts of CuSO4.5H2O added thereto and the mixture boiled until the excess ammonia was removed. Copper lsonicotinate which precipitated was removed by filtration and washed with hot water. It was then suspendedin water, 300 parts of a 17% sodium hydroxide solution added thereto and the mixture boiled for one hour. 10 parts of activated carbon were then added, the mixture boiled for one hour, an additional 10 parts of carbon added and boiling continued for ten minutes, at the end of which time the mixture was filtered and the filtrate made neutral to Brom Phenol Blue with hydrochloric acid. The isonicotinic acid which precipitated was removed by filtration, washed and dried. The resulting product melted at 316 C.

Example 13. parts of isoquinoline (M. P. 24.5 C.), 4.8 parts of selenium oxychloride and 920 parts of sulfuric acid were mixed and heated at a temperature between 280 and 290 C. for six hours in a vessel provided with an air condenser. At the end of this time the mixture was cooled, poured into crushed ice and partially neutralized with ammonium hydroxide, the quantity of ammonium hydroxide being insumcient to precipitate any of the reaction product; the selenium which separated was removed by filtration. The partially neutralized mixture was then boiled with 10 parts of activated carbon, filtered hot, and ammonium hydroxide added to the filtrate until the pH thereof was about 1.5; upon cooling to about 50 C. crystals appeared which were filtered ofi, washed with ice water and dried. The product obtained was cinchomeronic acid, melting at 253 C. to 256 C.

Example 14.A solution of 0.6 part of selenium and 85 parts of isoquinoline in 370 parts of 95% sulfuric acid was added to a solution of 0.9 parts of selenium in 920 parts of 95% sulfuric acid over a period of about two hours, the temperature being maintained at about 280 C. The temperature of the mixture was then maintained at 280 C. for an additional three hours. The cinchomeronic acid thus produced was isolated from the reaction mixture as described in Example 13.

Example 15.-A solution of 2.44 parts of selenium oxychloride and 85 parts of isoquinoline in 320 parts of 95% sulfuric acid was added to a solution of 2.44 parts of selenium oxychloride in 920 parts of 95% sulfuric acid over a period of about two hours, the temperature being maintained at about 280 C. The reaction mixture was then maintained at 280 C. for an additional thirty minutes. The cinchomeronic acid thus produced was recovered from the reaction mixture as described in Example 13.

It will be evident from the above description that my process provides an improved method of obtaining pyridine carboxylic acids from N-heteroaryl compounds employing a cheap and readily available oxidizing agent; in view thereof more economical production of the important nicotinic acid is made possible.

Since certain changes may be made in carrying out the above process without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

I claim:

1. A process for the oxidation of an N-heteroaryl compound having an oxidizable organic grouping attached to the nitrogen-containing aromatic nucleus by one or more carbon-to-carbon linkages to a compound containing a pyridine carboxylic acid radical, which comprises oxidizing said compound with sulfuric acid in the presence of a dissolved selenium compound, and recovering a compound containing a pyridine carboxylic acid radical.

2. A process for the oxidation of an N-heteroaryl compound having an oxidizable organic grouping attached to the nitrogen-containing aromatic nucleus by one or more carbon-to-carbon linkages to a compound containing a pyridine carboxylic acid radical, which comprises oxidizing said compound with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound at a temperature between about 200 and about 325 C., and recovering a compound containing a pyridine carboxylic acid radical.

3. A process for the oxidation of an N-heteroaryl compound having an oxidizable organic grouping attached to the nitrogen-containing aromatic nucleus by one or more carbon-to carbon linkages to a pyridine carboxylic acid, which comprises oxidizing said compound with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound at a temperature betweenabout 200 and about 325 C., and recovering the pyridine carboxylic acid produced.

4. A process for the production of nicotinic acid which comprises oxidizing quinoline with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound at a temperature between about 295 and about 315 0., and recovering the nlcotinic acid produced.

5. A process for the production of nicotinic acid which comprises subjecting a reaction mass acid and a relatively small amount of selenium oxychloride to a temperature between about 295 and about 315 C. until oxidation to nicotinic acid is substantially complete.

6. A process for the production of nicotinic acid which comprises oxidizing 3-picoline with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound at a temperature between about 305 and about 315 C., and recovering the nicotinic acid produced.

7. A process for the production of nicotinic acid which comprises subjecting a reaction mass formed by the admixture of B-picoline, sulfuric acid and a relatively small amount of selenium oxychloride to a temperature between about 305 and about 315 C. until oxidation to nicotinic acid is substantially complete.

8. A process for the production of cinchomeronic acid which comprises oxidizing isoquinoline with sulfuric acid. in the presence of a relatively small amount of a dissolved selenium compound.

9. A process for the production of oinchomeronic acid which comprises oxidizing isoquinoline formed by the admixture of quinoline, sulfuric 10 with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound at a temperature between about 200 and about 325 C., and recovering the cinchomeronic acid produced.

10. A process for the production of cinchomoronic acid which comprises subjecting a reaction mass formed by the admixture of isoquinoline, sulfuric acid and a relatively small amount of selenium oxychloride to a temperature between about 200 and about 325 C. until oxidation to cinchomeronic. acid is substantially complete.

11. A process for the oxidation of an N-heteroaryl compound having an oxidizable organic grouping attached to the nitrogen-containing aromatic nucleus by a carbon-to-carbon.linkage, which comprises oxidizing said compound with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound by heating a mixture of the major portion of the sulfuric acid reactant and about half the amount of the selenium compound to a temperature between about 200 and about 325 C., gradually adding to said mixture the remainder of the sulfuric acid and selenium compound admixed with the N-heteroaryl compound to be oxidized while maintaining the temperature ofthe mass between about 200 and about 325 C., then holding the reaction mixture at a temperature within this range until oxidation to the pyridine carboxylic acid has been completed, and recovering the pyridine carboxylic acid product.

12. A process for the production of nicotinic acid which comprises oxidizing quinollne with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound by heating a mixture of the major portion of the sulfuric acid reactant and about half the amount of the selenium compound to a temperature between about 295 and about 315 C., gradually adding to said mixture the remainder of the sulfuric acid and selenium compound admixed with the quinoline to be oxidized while maintaining the temperature of the mass between about 295 and about 315 C., then holding the reaction mixture at a temperature within this range until oxidation to nicotinic acid has been completed, converting the crude nicotinic acid to copper nicotinate by treatment with copper sulfate at a pH value between about 5 and about 7, treating the copper nicotinate with sodium hydroxide, adding acid to the sodium nicotinate solution formed to adjust its pH value to between about 3 and about 4, and cooling to recover nicotinic acid.

13. A process for the production of nicotinic acid which comprises oxidizing S-picoline with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound by heating a mixture of the major portion of the sulfuric acid reactant and about half the amount of the selenium compound to a temperature between about 305 and about 315 C., gradually adding to said mixture the remainder of the sulfuric acid and selenium compound admixed with the 3-picoline to be oxidized while maintaining the temperature of the mass between about 305 and about 315 C., then holding the reaction mixture at a temperature within this range until oxidation to nicotinic acid has been completed, converting the crude nicotinic acid to copper nicotinate by treatment with copper sulfate at a pH value between about 5 and about 7, treating the copper nicotinate with sodium hydroxide, adding acid to the sodium nicotinate a-iaaooo solution formed to adjust its pH value to between about 3 and about 4, and cooling to recover nicotinic acid.

14. A process for the production of cinchomeronic acid which comprises oxidizing isoquinoline with sulfuric acid in the presence of a relatively small amount of a dissolved selenium compound by heating a mixture of the major portion of the sulfuric acid reactant and about half the amount of the selenium compound to a temperature between about 200 and about 325 6..

gradually adding to said mixture the remainder of the sulfuric acid and selenium compound admixed with the isoquinoline to be oxidized while maintaining the temperature of the mass between about 200 and about 325 0., then holding the reaction mixture at a temperature within this range until oxidation to cinchomeronic acid has been completed, adjusting the pH value of the reaction mixture to between about 1 and about 2, and cooling to recover cinchomeronic acid.

15. In a process for the recovery of nicotinic acid from aqueous solutions thereof the steps which comprise adjusting the pH value of the solution to between about 3 and-about 4, and cooling to effect crystallization of the nicotinic acid.

16. In a process for the recovery of nicotinic acid from aqueous solutions thereof the steps which comprise adjusting the pH -value of the solution to between about 3.4 and about 3.6, and cooling to eifect crystallization of the nicotinic acid.

17. A process for the production of nicotinic acid which comprises oxidizing beta picoline' with sulfuric acid in the presence of a member selected from the group consisting of selenium and selenium containing compounds under such conditions to produce nicotinic acid.

18. A process for the production of a compound containing the nicotinic acid radical which comprises oxidizing quinoline with sulfuric acid in the presence of a member selected from the group consisting of selenium and selenium containing compounds and recovering a compound containing the nicotinic acid radical.

19. A process for the production of nicotinic acid which comprises oxidizing a 3-alkyl pyridine by heating with sulphuric acid in the presence of selenium under such conditions to produce nicotinic acid and recovering the nicotinic acid produced.

20. A process for the production of a compound containing the nicotinic acid radical which comprises oxidizing quinoline with sulfuric acid in the presence of a dissolved selenium compound and recovering a compound containing the nicotinic acid radical.

21. A process for the production of a compound containing the nicotinic acid radical which comprises oxidizing an N-heteroaryl compound hav- REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Name Date Number Siebert Sept. 15, 1942 

